Investigation of fullerenol-induced changes in poroelasticity of human hepatocellular carcinoma by AFM-based creep tests

In this study, atomic force microscopy (AFM) is used to investigate the alterations of the poroelastic properties of hepatocellular carcinoma (SMMC-7721) cells treated with fullerenol. The SMMC-7721 cells were subject to AFM-based creep tests, and a corresponding poroelastic indentation model was used to determine the poroelastic parameters by curve fitting. Comparative analyses indicated that the both permeability and diffusion of fullerenol-treated cells increased significantly while their elastic modulus decreased by a small amount. From the change in the trend of the determined parameter, we verified the corresponding alternations of cytoskeleton (mainly filaments actin), which was reported by the previous study using confocal imaging method. Our investigation on SMMC-7721 cell reveals that the poroelastic properties could provide a better understanding how the cancer cells are affected by fullerenol or potentially other drugs which could find possible applications in drug efficacy test, cancer diagnosis and secure therapies.     

Copy-number variation introduced by long transgenes compromises mouse male fertility independently of pachytene checkpoints

Chromosoma - Long transgenes are often used in mammalian genetics, e.g., to rescue mutations in large genes. In the course of experiments addressing the genetic basis of hybrid sterility caused by...     

The patients with clinically isolated syndrome and relapsing remitting multiple sclerosis show different levels of advanced protein oxidation products and total thiol content in plasma and CSF

Advanced oxidation protein products (AOPP) and total thiol (SH) groups levels in plasma and CSF were studied in a cohort of 50 clinically isolated syndrome (CIS) and 57 relapsing remittent multiple sclerosis (RRMS) patients related to 20 control group (CG) patients’ values. The obtained results were compared regarding patients demographic, biochemical, clinical (EDSS) and MRI features (total T2 weighted lesions number and Gd enhancement lesion volume).     

Improved Detection of Common Variants Associated with Schizophrenia by Leveraging Pleiotropy with Cardiovascular-Disease Risk Factors

Several lines of evidence suggest that genome-wide association studies (GWASs) have the potential to explain more of the “missing heritability” of common complex phenotypes. However, reliable methods for identifying a larger proportion of SNPs are currently lacking. Here, we present a genetic-pleiotropy-informed method for improving gene discovery with the use of GWAS summary-statistics data. We applied this methodology to identify additional loci associated with schizophrenia (SCZ), a highly heritable disorder with significant missing heritability. Epidemiological and clinical studies suggest comorbidity between SCZ and cardiovascular-disease (CVD) risk factors, including systolic blood pressure, triglycerides, low- and high-density lipoprotein, body mass index, waist-to-hip ratio, and type 2 diabetes. Using stratified quantile-quantile plots, we show enrichment of SNPs associated with SCZ as a function of the association with several CVD risk factors and a corresponding reduction in false discovery rate (FDR). We validate this “pleiotropic enrichment” by demonstrating increased replication rate across independent SCZ substudies. Applying the stratified FDR method, we identified 25 loci associated with SCZ at a conditional FDR level of 0.01. Of these, ten loci are associated with both SCZ and CVD risk factors, mainly triglycerides and low- and high-density lipoproteins but also waist-to-hip ratio, systolic blood pressure, and body mass index. Together, these findings suggest the feasibility of using genetic-pleiotropy-informed methods for improving gene discovery in SCZ and identifying potential mechanistic relationships with various CVD risk factors.     

Establishment and inaugural meeting of the Australian and New Zealand Purine Club

Purinergic Signalling -     

Immune competence and spleen size scale with colony status in the naked mole-rat

Naked mole-rats (NM-R; Heterocephalus glaber) live in multi-generational colonies with a social hierarchy, and show low cancer incidence and long life-spans. Here we asked if an immune component might underlie such extreme physiology. The largest lymphoid organ is the spleen, which plays an essential role in responding to immunological insults and may participate in combating cancer and slowing ageing. We investigated the anatomy, molecular composition and function of the NM-R spleen using RNA-sequencing and histological analysis in healthy NM-Rs. Spleen size in healthy NM-Rs showed considerable inter-individual variability, with some animals displaying enlarged spleens. In all healthy NM-Rs, the spleen is a major site of adult haematopoiesis under normal physiological conditions. However, myeloid-to-lymphoid cell ratio is increased and splenic marginal zone showed markedly altered morphology when compared to other rodents. Healthy NM-Rs with enlarged spleens showed potentially better anti-microbial profiles and were much more likely to have a high rank within the colony. We propose that the anatomical plasticity of the spleen might be regulated by social interaction and gives immunological advantage to increase the lifespan of higher-ranked animals.     

Combinations of Genetic Data Present in Bipolar Patients,but Absent in Control Persons

The main objective of the study was to find combinations of genetic variants significantly associated with bipolar disorder. In a previous study of bipolar disorder, combinations of three single nucleotide polymorphism (SNP) genotypes taken from 803 SNPs were analyzed, and four clusters of combinations were found to be significantly associated with bipolar disorder. In the present study, combinations of four SNP genotypes taken from the same 803 SNPs were analyzed, and one cluster of combinations was found to be significantly associated with bipolar disorder. Combinations from the new cluster and from the four previous clusters were identified in the genomes of 209 of the 607 patients in the study whereas none of the 1355 control participants had any of these combinations in their genome.     

β-Lactam and glycopeptide antibiotics: first and last line of defense?

Most infections are caused by bacteria, many of which are ever-evolving and resistant to nearly all available antibiotics. β-Lactams and glycopeptides are used to combat these infections by inhibiting bacterial cell-wall synthesis. This mechanism remains an interesting target in the search for new antibiotics in light of failed genomic approaches and the limited input of major pharmaceutical companies. Several strategies have enriched the pipeline of bacterial cell-wall inhibitors; examples include combining screening strategies with lesser-explored microbial diversity, or reinventing known scaffolds based on structure-function relationships. Drugs developed using novel strategies will contribute to the arsenal in fight against the continued emergence of bacterial resistance.